T cells with increased responsiveness cause obesity in mice without diet intervention

Ida Gregersen; Xiang Y Kong; Sander Kooijman; Håvard Foyn; Helene Grannes; Maria B Olsen; Anna M Lone; Kuan Yang; Ana Quiles-Jiménez; Marianne Tran; Jonas Øgaard; Filip M Segers; Azita Rashidi; Ellen Lund Sagen; Knut H Lauritzen; Amanda C M Pronk; Jan Freark de Boer; Kirsten B Holven; Espen Melum; Pål Aukrust; Kjetil Taskén; Sverre Holm; Patrick C N Rensen; Tuva B Dahl; Bente Halvorsen

doi:10.1016/j.isci.2024.109471

T cells with increased responsiveness cause obesity in mice without diet intervention

iScience. 2024 Mar 11;27(4):109471. doi: 10.1016/j.isci.2024.109471. eCollection 2024 Apr 19.

Authors

Ida Gregersen¹, Xiang Y Kong¹, Sander Kooijman^{2

3}, Håvard Foyn^{1

4}, Helene Grannes^{1

5}, Maria B Olsen^{1

5}, Anna M Lone^{4

6}, Kuan Yang¹, Ana Quiles-Jiménez¹, Marianne Tran¹, Jonas Øgaard¹, Filip M Segers¹, Azita Rashidi¹, Ellen Lund Sagen^{1

5}, Knut H Lauritzen^{1

5}, Amanda C M Pronk^{2

3}, Jan Freark de Boer⁷, Kirsten B Holven^{8

9}, Espen Melum^{1

5

10

11

12}, Pål Aukrust^{1

5}, Kjetil Taskén^{4

6}, Sverre Holm¹, Patrick C N Rensen^{2

3}, Tuva B Dahl^{1

13}, Bente Halvorsen^{1

5

14}

Affiliations

¹ Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway.
² Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands.
³ Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.
⁴ Department of Cancer Immunology, Institute of Cancer Research, Oslo University Hospital, 0424 Oslo, Norway.
⁵ Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
⁶ K.G. Jebsen Centre for B Cell Malignancies, Institute of Clinical Medicine, University of Oslo, 0317 Oslo, Norway.
⁷ University Medical Center Groningen, Department of Pediatrics, Section Molecular Metabolism & Nutrition, Department of Laboratory Medicine, Groningen, the Netherlands.
⁸ Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
⁹ Norwegian National Advisory Unit on Familial Hypercholesterolemia, Oslo University Hospital, Oslo, Norway.
¹⁰ Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.
¹¹ Section of Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.
¹² Hybrid Technology Hub-Centre of Excellence, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
¹³ Department of Research and Development, Division of Emergencies and Critical Care, Oslo University Hospital HF, Rikshospitalet, Oslo, Norway.
¹⁴ Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Abstract

Obesity is a complex multicausal disease that can cause morbidity and mortality, and there is need for improved knowledge on the underlying mechanisms. Using a mouse model of increased T cell responsiveness, we show that development of obesity can be driven by immune cells. This was confirmed with bone marrow transplantation and adoptive T cell transfer to several recipient mouse models. Single-cell RNA sequencing and CyTOF analysis showed that the mice display altered composition of circulating T cells and increased T cell activation in visceral adipose tissue, suggesting activated T cells as critical players in the increased fat mass. In this study, we provide evidence that obesity can be driven by immune cell activity and in particular by T cells, which could have broad implications for prevention and treatment of this condition.

Keywords: Immunology; Nutrition.